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  1. Article ; Online: Scaled, high fidelity electrophysiological, morphological, and transcriptomic cell characterization.

    Lee, Brian R / Budzillo, Agata / Hadley, Kristen / Miller, Jeremy A / Jarsky, Tim / Baker, Katherine / Hill, DiJon / Kim, Lisa / Mann, Rusty / Ng, Lindsay / Oldre, Aaron / Rajanbabu, Ram / Trinh, Jessica / Vargas, Sara / Braun, Thomas / Dalley, Rachel A / Gouwens, Nathan W / Kalmbach, Brian E / Kim, Tae Kyung /
    Smith, Kimberly A / Soler-Llavina, Gilberto / Sorensen, Staci / Tasic, Bosiljka / Ting, Jonathan T / Lein, Ed / Zeng, Hongkui / Murphy, Gabe J / Berg, Jim

    eLife

    2021  Volume 10

    Abstract: The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual neurons. To generate Patch-seq datasets at scale, we ... ...

    Abstract The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual neurons. To generate Patch-seq datasets at scale, we identified and refined key factors that contribute to the efficient collection of high-quality data. We developed patch-clamp electrophysiology software with analysis functions specifically designed to automate acquisition with online quality control. We recognized the importance of extracting the nucleus for transcriptomic success and maximizing membrane integrity during nucleus extraction for morphology success. The protocol is generalizable to different species and brain regions, as demonstrated by capturing multimodal data from human and macaque brain slices. The protocol, analysis and acquisition software are compiled at https://githubcom/AllenInstitute/patchseqtools. This resource can be used by individual labs to generate data across diverse mammalian species and that is compatible with large publicly available Patch-seq datasets.
    MeSH term(s) Animals ; Brain ; Electrophysiological Phenomena ; Humans ; Macaca mulatta ; Mice ; Neurons/cytology ; Neurons/physiology ; Patch-Clamp Techniques ; Single-Cell Analysis/methods ; Software ; Transcriptome
    Language English
    Publishing date 2021-08-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.65482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

    Sorensen, Staci A / Gouwens, Nathan W / Wang, Yun / Mallory, Matt / Budzillo, Agata / Dalley, Rachel / Lee, Brian / Gliko, Olga / Kuo, Hsien-Chi / Kuang, Xiuli / Mann, Rusty / Ahmadinia, Leila / Alfiler, Lauren / Baftizadeh, Fahimeh / Baker, Katherine / Bannick, Sarah / Bertagnolli, Darren / Bickley, Kris / Bohn, Phil /
    Brown, Dillan / Bomben, Jasmine / Brouner, Krissy / Chen, Chao / Chen, Kai / Chvilicek, Maggie / Collman, Forrest / Daigle, Tanya / Dawes, Tim / de Frates, Rebecca / Dee, Nick / DePartee, Maxwell / Egdorf, Tom / El-Hifnawi, Laila / Enstrom, Rachel / Esposito, Luke / Farrell, Colin / Gala, Rohan / Glomb, Andrew / Gamlin, Clare / Gary, Amanda / Goldy, Jeff / Gu, Hong / Hadley, Kristen / Hawrylycz, Mike / Henry, Alex / Hill, Dijon / Hirokawa, Karla E / Huang, Zili / Johnson, Katelyn / Juneau, Zoe / Kebede, Sara / Kim, Lisa / Lee, Changkyu / Lesnar, Phil / Li, Anan / Li, Yaoyao / Liang, Elizabeth / Link, Katie / Maxwell, Michelle / McGraw, Medea / McMillen, Delissa A / Mukora, Alice / Ng, Lindsay / Ochoa, Thomas / Oldre, Aaron / Park, Daniel / Pom, Christina Alice / Popovich, Zoran / Potekhina, Lydia / Rajanbabu, Ram / Ransford, Shea / Reding, Melissa / Ruiz, Augustin / Sandman, David / Siverts, La'Akea / Smith, Kimberly A / Stoecklin, Michelle / Sulc, Josef / Tieu, Michael / Ting, Jonathan / Trinh, Jessica / Vargas, Sara / Vumbaco, Dave / Walker, Miranda / Wang, Micheal / Wanner, Adrian / Waters, Jack / Williams, Grace / Wilson, Julia / Xiong, Wei / Lein, Ed / Berg, Jim / Kalmbach, Brian / Yao, Shenqin / Gong, Hui / Luo, Qingming / Ng, Lydia / Sümbül, Uygar / Jarsky, Tim / Yao, Zizhen / Tasic, Bosiljka / Zeng, Hongkui

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include ...

    Abstract The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.
    Language English
    Publishing date 2023-11-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.25.568393
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

    Lee, Brian R / Dalley, Rachel / Miller, Jeremy A / Chartrand, Thomas / Close, Jennie / Mann, Rusty / Mukora, Alice / Ng, Lindsay / Alfiler, Lauren / Baker, Katherine / Bertagnolli, Darren / Brouner, Krissy / Casper, Tamara / Csajbok, Eva / Donadio, Nicholas / Driessens, Stan L W / Egdorf, Tom / Enstrom, Rachel / Galakhova, Anna A /
    Gary, Amanda / Gelfand, Emily / Goldy, Jeff / Hadley, Kristen / Heistek, Tim S / Hill, Dijon / Hou, Wen-Hsien / Johansen, Nelson / Jorstad, Nik / Kim, Lisa / Kocsis, Agnes Katalin / Kruse, Lauren / Kunst, Michael / León, Gabriela / Long, Brian / Mallory, Matthew / Maxwell, Michelle / McGraw, Medea / McMillen, Delissa / Melief, Erica J / Molnar, Gabor / Mortrud, Marty T / Newman, Dakota / Nyhus, Julie / Opitz-Araya, Ximena / Ozsvár, Attila / Pham, Trangthanh / Pom, Alice / Potekhina, Lydia / Rajanbabu, Ram / Ruiz, Augustin / Sunkin, Susan M / Szöts, Ildikó / Taskin, Naz / Thyagarajan, Bargavi / Tieu, Michael / Trinh, Jessica / Vargas, Sara / Vumbaco, David / Waleboer, Femke / Walling-Bell, Sarah / Weed, Natalie / Williams, Grace / Wilson, Julia / Yao, Shenqin / Zhou, Thomas / Barzó, Pál / Bakken, Trygve / Cobbs, Charles / Dee, Nick / Ellenbogen, Richard G / Esposito, Luke / Ferreira, Manuel / Gouwens, Nathan W / Grannan, Benjamin / Gwinn, Ryder P / Hauptman, Jason S / Hodge, Rebecca / Jarsky, Tim / Keene, C Dirk / Ko, Andrew L / Korshoej, Anders Rosendal / Levi, Boaz P / Meier, Kaare / Ojemann, Jeffrey G / Patel, Anoop / Ruzevick, Jacob / Silbergeld, Daniel L / Smith, Kimberly / Sørensen, Jens Christian / Waters, Jack / Zeng, Hongkui / Berg, Jim / Capogna, Marco / Goriounova, Natalia A / Kalmbach, Brian / de Kock, Christiaan P J / Mansvelder, Huib D / Sorensen, Staci A / Tamas, Gabor / Lein, Ed S / Ting, Jonathan T

    Science (New York, N.Y.)

    2023  Volume 382, Issue 6667, Page(s) eadf6484

    Abstract: Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq ( ... ...

    Abstract Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.
    MeSH term(s) Animals ; Humans ; Mice ; Electrophysiological Phenomena ; GABAergic Neurons/metabolism ; gamma-Aminobutyric Acid/metabolism ; Interneurons/metabolism ; Neocortex/cytology ; Neocortex/metabolism ; Patch-Clamp Techniques
    Chemical Substances gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adf6484
    Database MEDical Literature Analysis and Retrieval System OnLINE

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